<  Retour au portail Polytechnique Montréal

Non-alcoholic fatty liver disease, and the underlying altered fatty acid metabolism, reveals brain hypoperfusion and contributes to the cognitive decline in APP/PS1 mice

Anthony Pinçon, Olivia De Montgolfier, Nilay Akkoyunlu, Caroline Daneault, Philippe Pouliot, Louis Villeneuve, Frédéric Lesage, Bernard I. Levy, Nathalie Thorin-Trescases, Éric Thorin et Matthieu Ruiz

Article de revue (2019)

Document en libre accès dans PolyPublie et chez l'éditeur officiel
[img]
Affichage préliminaire
Libre accès au plein texte de ce document
Version officielle de l'éditeur
Conditions d'utilisation: Creative Commons: Attribution (CC BY)
Télécharger (882kB)
Afficher le résumé
Cacher le résumé

Abstract

Non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver disease, is associated with cognitive decline in middle-aged adults, but the mechanisms underlying this association are not clear. We hypothesized that NAFLD would unveil the appearance of brain hypoperfusion in association with altered plasma and brain lipid metabolism. To test our hypothesis, amyloid precursor protein/presenilin-1 (APP/PS1) transgenic mice were fed a standard diet or a high-fat, cholesterol and cholate diet, inducing NAFLD without obesity and hyperglycemia. The diet-induced NAFLD disturbed monounsaturated and polyunsaturated fatty acid (MUFAs, PUFAs) metabolism in the plasma, liver, and brain, and particularly reduced n-3 PUFAs levels. These alterations in lipid homeostasis were associated in the brain with an increased expression of Tnfalpha, Cox2, p21, and Nox2, reminiscent of brain inflammation, senescence, and oxidative stress. In addition, compared to wild-type (WT) mice, while brain perfusion was similar in APP/PS1 mice fed with a chow diet, NAFLD in APP/PS1 mice reveals cerebral hypoperfusion and furthered cognitive decline. NAFLD reduced plasma beta40- and beta42-amyloid levels and altered hepatic but not brain expression of genes involved in beta-amyloid peptide production and clearance. Altogether, our results suggest that in a mouse model of Alzheimer disease (AD) diet-induced NAFLD contributes to the development and progression of brain abnormalities through unbalanced brain MUFAs and PUFAs metabolism and cerebral hypoperfusion, irrespective of brain amyloid pathology that may ultimately contribute to the pathogenesis of AD.

Mots clés

Alzheimer disease mouse model; Nafld; amyloid Beta; brain hypoperfusion; inflammation; liver-to-brain axis; polyunsaturated fatty acids; senescence; untargeted and targeted lipidomics

Sujet(s): 2500 Génie électrique et électronique > 2500 Génie électrique et électronique
6400 Recherche en sciences de la vie liées à la santé publique et aux maladies humaines > 6401 Pathologie
Département: Département de génie électrique
Organismes subventionnaires: Canadian Institutes of Health Research, Heart and Stroke foundation of Canada (E.T.), Foundation of the Montreal Heart Institute (E.T.), Fonds de la recherche du Québec-Santé (FRQS)
Numéro de subvention: 4496, 133649
URL de PolyPublie: https://publications.polymtl.ca/5088/
Titre de la revue: Metabolites (vol. 9, no 5)
Maison d'édition: MDPI
DOI: 10.3390/metabo9050104
URL officielle: https://doi.org/10.3390/metabo9050104
Date du dépôt: 04 août 2022 15:12
Dernière modification: 12 avr. 2024 01:37
Citer en APA 7: Pinçon, A., De Montgolfier, O., Akkoyunlu, N., Daneault, C., Pouliot, P., Villeneuve, L., Lesage, F., Levy, B. I., Thorin-Trescases, N., Thorin, É., & Ruiz, M. (2019). Non-alcoholic fatty liver disease, and the underlying altered fatty acid metabolism, reveals brain hypoperfusion and contributes to the cognitive decline in APP/PS1 mice. Metabolites, 9(5), 20 pages. https://doi.org/10.3390/metabo9050104

Statistiques

Total des téléchargements à partir de PolyPublie

Téléchargements par année

Provenance des téléchargements

Dimensions

Actions réservées au personnel

Afficher document Afficher document